“Sol-gel” processes are generally used to fabricate porous materials including self-assembled films. A sol is a liquid solution containing a colloid suspension of a material of interest dissolved in an appropriate solvent. Condensation reactions between the dissolved precursor molecules result in structures (particles, branched chains, linear chains, etc.) forming within the sol. The size, growth rate and morphology of these structures depend on the kinetics of the reactions within the solvent, which in turn are determined by parameters such as solution concentration, amount of water present, the temperature and pH of the solvent, agitation of the solvent and other parameters. Given enough time, condensation reactions will lead to the aggregation of growing particles or chains until eventually, a gel is formed. The gel can be visualized as a very large number of cross-linked precursor molecules forming a continuous, macroscopic-scale, solid phase, which encloses a continuous liquid phase consisting of the remaining solution. In the final steps of the sol-gel process, the enclosed solvent is removed (generally by drying) and the precursor molecules cross-link (a process called aging) resulting in the desired solid.
Sol-gel synthesis of materials offers several advantages over other synthetic routes. These advantages can include mild processing conditions (low temperature, low pressure, mild pH), inexpensive raw materials, no need for vacuum processing or other expensive equipment, and a high level of control over the resulting structure, particularly as it pertains to porosity. Regarding shape of the final product, there is essentially no limitation, because the liquid sol can be cast in any conceivable form before allowed to gel, including monoliths, thin films, fibers and micro- or nano-scale particles.
Porosity of materials produced in sol-gel processes can be controlled in a number of different ways. In the simplest sol-gel process, no special porogen is added to the sol and the porosity of the final solid is determined by the amount of precursor branching or aggregation before gelling. Average pore size, volume and surface area of porous sol-gel compositions increase with the size of the precursor molecules prior to the sol-gel processing.
Porosity can also be manipulated by the presence of additional materials within the solvent during the sol-gel process. The incorporation of sacrificial porogens in the sol (particularly those that can be easily removed via heating or other methods), is generally viewed as an efficient method to obtain porous solids when using sol-gel processes. Historically, these efforts were focused upon the fabrication of low dielectric constant (low-k) insulating films for the microelectronics industry. Sacrificial templates can also be used to create pores in inorganic materials formed using sol-gel processes. Sacrificial templates are usually amphiphilic molecules (i.e. those having hydrophilic and hydrophobic properties) capable of self-assembling in solution. These amphiphilic molecules create a highly-ordered structure that guides the precursor molecules to co-assemble around the structure. Once the precursor molecules co-assemble around the structure, it can be removed, leaving a negative image void.
Porous materials made using sol-gel processes can be used to deliver bioactive materials. For example, Vallet-Regi et al. (Chem. Mater. 2001, 13, 308-311) described charging powdered MCM-41 with ibuprofen. In this case, the ibuprofen was loaded into MCM-41 by dissolving the ibuprofen in hexane and adding the MCM-41 compound to the hexane in a powdered form. Munoz et al. (Chem. Mater. 2003, 15 500-503) described an experiment which demonstrated that ibuprofen could be delivered at a different rate from two different formulations of MCM-41, one made using a 16 carbon surfactant and one made using a 12 carbon surfactant.
Prior to International Patent Application Number PCT/US2004/040270 (PCT '270), which is fully incorporated by reference herein, no reference described an deployable medical device or bioactive material delivery device comprising a triblock copolymer template-based sol-gel composition formed surface coating with substantially continuously interconnected channels designed to function as a bioactive material reservoir. Moreover, no reference described a triblock copolymer template-based sol-gel composition surface coating with bioactive material found within the coating itself before being applied to the surface of a deployable medical device as well as having substantially continuously interconnected channels that could further function as a bioactive material reservoir after being applied to the surface of a deployable medical device. Thus, the invention described in PCT '270 provided at least two additional mechanisms through which bioactive materials could be loaded onto the surface of a deployable medical device.
While the materials and methods described in PCT '270 provided a number of important benefits (described therein), there is still room for improvement in the creation of bioactive material carrying materials made with sol-gel processes. For instance, better control of bioactive material particles during sol-gel processing and after device deployment could provide a benefit in allowing more accurate control over the amount of bioactive materials within a particular sol-gel composition as well as more control over the release rate of bioactive materials from a deployed medical device into the physiological environment after device deployment. The present disclosure provides such benefits. Before describing these benefits in more detail, however, background relating to a further aspect of the present invention is described.
The contents of US 2007/0071789 are herein incorporated by reference in its entirety. US 2007/0071789 describes implantable medical devices employing sol-gel composition coatings that function as a bioactive material reservoir, and the use of sol-gel composition coatings for improved adhesion of organic and inorganic substrates. The contents of U.S. application Ser. No. 10/528,577 also are herein incorporated by reference in its entirety. Ser. No. 10/528,577 describes medical devices that release drugs for the selective therapy of specific diseased tissues or organ parts, characterized in that lipophilic, largely water-insoluble drugs that bind to any tissue components adhere to the surfaces of devices that come into contact with the diseased tissue by being pressed against it at least for a short time and immediately release the active agent when in contact with tissue.
WO 2007/092043 describes implantable medical devices employing sol-gel composition coatings that functions as a bioactive material reservoir, and the use of sol-gel composition coatings for improved adhesion of organic and inorganic substrates. U.S. Pat. No. 6,764,690 discloses controllably dissolvable silica-xerogels prepared via a sol-gel process and a delivery device including controllably dissolvable silica-xerogel into which structure a bioactive material is incorporated. U.S. Pat. No. 6,544,223 discloses a device for delivering therapeutic agents and methods of making such a device. The device disclosed includes an inflatable balloon having holes in the walls of the balloon. U.S. Pat. No. 7,115,299 discloses inflatable porous balloons secured at a distal end of a catheter-based device with a composition including a polymer applied to the outer surface of the balloon.
U.S. Pat. No. 6,524,274 relates to a method for delivering a drug to tissue within the body by providing a catheter constructed for insertion in the body which carries a hydrogel. U.S. Pat. No. 7,066,904 relates to a catheter constructed for insertion in the body with a catheter shaft having an expandable hydrogel-coated porous balloon portion mounted on the catheter shaft. One of the disadvantages associated with U.S. Pat. No. 6,524,274 and U.S. Pat. No. 7,066,904 is that a separate or custom pH solution has to be mixed for inflation of the balloon. This would be too cumbersome. There also would be different inflation media versus the body pH or saline.
One challenge in the field of deployable medical devices has been adhering bioactive materials and bioactive material-containing coatings to the surfaces of deployable devices so that the bioactive materials will be released over time once the device is deployed. One approach to adhering bioactive materials to substrates, such as the surface of deployable medical devices has been to include the bioactive materials in polymeric coatings. Polymeric coatings can hold bioactive materials onto the surface of deployable medical devices, and release the bioactive materials via degradation of the polymer or diffusion into liquid or tissue (in which case the polymer is non-degradable). While polymeric coatings can be used to adhere bioactive materials to deployed medical devices, there are problems associated with their use. One problem is that adherence of a polymeric coating to a substantially different substrate, such as a stent's metallic substrate, is difficult due to differing characteristics of the materials (such as differing thermal expansion properties). Further, most inorganic solids are covered with a hydrophilic native surface oxide that is characterized by the presence of surface hydroxyl groups (M-OH, where M represents an atom of the inorganic material, such as silicon or aluminum). At ambient conditions then, at least a monolayer of adsorbed water molecules covers the surface, forming hydrogen bonds with these hydroxyl groups. Therefore, due to this water layer, hydrophobic organic polymers cannot spontaneously adhere to the surface of the deployable medical device. Furthermore, even if polymer/surface bonds (including covalent bonds) are formed under dry conditions, those bonds are susceptible to hydrolysis (i.e. breakage) upon exposure to water. This effect is particularly important in applications where devices or components containing organic/inorganic interfaces must operate in aqueous, corrosive environments such as a human or other animal's body. These difficulties associated with adhering two different material types often leads to inadequate bonding between the deployable medical device and the overlying polymeric coating which can result in the separation of the materials over time. Such separation is an exceptionally undesirable property in a deployed medical device.
Two different approaches have traditionally been followed to reinforce organic/inorganic interfaces. The first is the introduction of controlled roughness or porosity on an inorganic surface that induces polymer mechanical interlocking. The second is chemical modification of the inorganic surface via amphiphilic silane coupling agents that improve polymer wetting, bonding and interface resistance to water. While these methods provide some benefits, they are not effective in all circumstances. Thus, there is room for improvement in methods associated with adhering inorganic and organic surfaces. Certain sol-gel composition embodiments according to the present invention provide such improvements.
Paclitaxel coated catheters can have long inflation times. They can also have contra-indicated ischemic plots, proximal lesions/left main coronary artery and a high degree of washout which can be greater than 80%. Weeping catheters/balloons can also have long inflation times with a high degree of washout which can be greater than 95%. Dual balloons can also have long inflation times and be traumatic to a healthy vessel. There is a need for a drug eluting medical device which has an expandable member coated with sol gel technology, which overcomes the shortcomings of prior art devices.
US 2006/0020243 describes a paclitaxel coated catheter which has disadvantages. One is that it has long inflation times. Clinical trials required one minute inflation time. This long inflation time limits the population which can be treated and can lead to ischemic events. Embodiments according to the present disclosure utilize perfusion whereas US 2006/0020243 does not. Perfusion provides the improvement which would reduce ischemic event. Also, the devices according to US 2006/0020243 have a high degree of drug washout due to poor coating. The present disclosure relates to devices which overcome the disadvantages of prior art devices and methods such as disclosed in US 2006/0020243.